Mucociliary transport in respiratory systems serves as a primary line of defense in combating respiratory infections. Dysfunction of mucociliary clearance may result either from impaired cilia or abnormalities in the fluid component, with important health consequences. The long term objective of the proposed research is to determine how respiratory cilia are regulated in order to better define the etiology of various disease processes and to seek means of stimulating mucociliary clearance when impaired. The aims of this proposal are to utilize key features of the lung mucociliary epithelium from the newt, Taricha granulosa, to focus on two neglected areas of respiratory ciliary function: the regulation of their waveforms and coordination. Ciliary beat frequency varies in a characteristic manner in each of the following opposing experimental conditions: 1) normal vs outer dynein arm depleted axonemes; 2) unactivated vs activated axonemes and 3) cilia subjected to low vs high mechanical load. The waveforms of cilia resulting from these treatments will be photographed, manually digitized and analyzed by existing computer modeling techniques to define ciliary bending parameters that can be used to ascertain how ciliary beat frequency is modulated. The newt lung mucociliary epithelium is not uniform with respect to its transport properties. Rather, it appears to be divided into discrete, functionally coordinated domains. Each domain behaves as though it contains one or more "primary oscillator cells" at one end that is responsible for initiating metachronal waves. We will probe the nature of this coordination mechanism and study the structural and functional properties of a subset of cold/drug stable microtubules that appear largely responsible for maintaining the alignment and coordination of cilia.